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How Metal Ions Affect Amyloid Formation: Cu 2+ ‐ and Zn 2+ ‐Sensitive Peptides
Author(s) -
Pagel Kevin,
Seri Tomomi,
von Berlepsch Hans,
Griebel Jan,
Kirmse Reinhard,
Böttcher Christoph,
Koksch Beate
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200700656
Subject(s) - chemistry , metal , metal ions in aqueous solution , ion , copper , zinc , bioinorganic chemistry , amyloid (mycology) , inorganic chemistry , radiochemistry , biochemistry , organic chemistry
Abstract The common feature of proteins involved in many neurodegenerative diseases is their ability to adopt at least two different stable conformations. The conformational transition that shifts the equilibrium from the functional, mostly partially α‐helical structure, to the β‐sheet rich amyloid can be triggered by numerous factors, such as mutations in the primary structure or changes in the environment. We present a set of model peptides that, without changes in their primary structure, react in a predictable fashion in the presence of transition metal ions by adopting different conformations and aggregate morphologies. These de novo designed peptides strictly follow the characteristic heptad repeat of the α‐helical coiled‐coil structural motif. Furthermore, domains that favor β‐sheet formation have been incorporated to make the system prone to amyloid formation. As a third feature, histidine residues create sensitivity towards the presence of transition metal ions. CD spectroscopy, ThT fluorescence experiments, and transmission electron microscopy were used to characterize peptide conformation and aggregate morphology in the presence of Cu 2+ and Zn 2+ . Furthermore, the binding geometry within peptide–Cu 2+ complexes was characterized by electron paramagnetic resonance spectroscopy.